The broad objective of the proposed research is the elucidation of the pathways of formation, the structural, electronic, and reactivity properties, and the physiological functions of the metal-containing coordination sites of iron-sulfur proteins and enzymes. The methodology is that of the synthetic analogue approach to the active sites of metallobiomolecules, whereby low molecular weight site representations are prepared and their properties scrutinized at the small molecule level of detail. These problems will be undertaken: (1) synthesis of cyclic polythiol ligands designed to stabilize certain core structures and oxidation levels. [Fe-mS-n]z, (2) synthesis and characterization of [Fe2S2]1+ and [Fe4S4]3+ clusters in order to determine detailed structures and electron delocalization properties; (3) synthesis and characterization of the trinuclear clusters [Fe3S4]1+,O with the main intentions of providing a structure proof for protein Fe3S4 clusters and examining cluster reconstitution reactions, (4) synthesis of double-cubane clusters for the purpose of assessing intramolecular electronic interactions; (5) synthesis and characterization of Fe4S4 clusters specifically functionalized at one ligand site; (6) elucidation of the reaction sequence leading to the formation of the reduced ferredoxin analogues [Fe4S4(SR)4]3-, (7) definition of the intrinsic core structural change accompanying the biologically pervasive [Fe4S4]2+,1+ electron transfer reaction; (8) development of a structural and functional model of the active sites of sulfite and nitrite reductase, including examination of reduced substrate intermediates by synthesis, (9) synthesis and characterization of complexes containing the [Fe2S]3+,4+,5+ bridge unit similar to that in sulfidohemerythrin; (10) continued development of metal-thiolate chemistry, with emphasis on the geometrical and electronic structures and reactivities of [M(SR)4]1-,2- and [M2(SR)6]2- species.